3D pancreatic tumor spheroids co-cultured with stromal cells in an organ on a chip

A recent paper from Jang et al. from Kuh’s lab at the Catholic University of Korea co-culturing pancreatic cancer cells with fibroblasts and macrophages to create a 3D tumor on a chip model. The paper evaluates the culture of the cancer cells with and without the stromal cells and studies the anti-invasive activity and cell-type dependent cytotoxicity of chemotherapeutic drugs.

Authors found that epithelial-mesenchymal transition (EMT) related protein in pancreatic tumor spheroids is increased when co-cultured with stromal cell. Furthermore, after treatment with 4 drugs, Gemcitabine ,5-fluorouracil, Oxaliplatin, and Paclitaxel, the authors concluded that cell viability and invasiveness depended on the drug and its dosage.

Organ on a chip, Tissue chip, Microphysiological systems, Tumor Micro-environment,
3D co-culture, microfluidics, pdms, invasion, Migration, drug resistance, cell cytotoxicity, cell-cell interaction, epithelial mesenchymal transition, emt

Digestible of the paper Jang, S.-D., et al. (2021). “Anti-cancer activity profiling of chemotherapeutic agents in 3D co-cultures of pancreatic tumor spheroids with cancer-associated fibroblasts and macrophages.” Cancers 13(23): 5955. This paper is reproduced under https://creativecommons.org/licenses/by/4.0/. The image of the chip was edited for better clarity, data in the table and text were compiled and interpreted by AZAR Innovations.

Authors used a
side-by-side channel chip, cells (pancreatic tumor spheroids with aPSCs and THP-1-derived M2 macrophages (M2 THP-1 cells) ) were suspended in type I collagen solution
Fabrication method:
Soft lithography with PDMS
Sterilization method:
Cell incorporation: Cell-collagen mixture were injected into each channel
On-chip read-outs:
On-chip monitoring, End-point microscopy, Live-dead staining

Strong points:
+ 3D co-culture of tumor spheroids with stromal cell

+ Study of different drugs with different concentration
+ Analyzing 3D spatial and temporal heterogeneity of subpopulation
+ Compartmentalized chip

Nothing is perfect! The system can also improve:
– The same old story, PDMS but no investigation on the real concentration that the organoids are exposed to and what fraction of the drug is absorbed into PDMS
-They used cancer and monocytic cell lines
-No automatic perfusion, cell culture was refreshed by hand

Conclusion and outlook
The 3D Tumor microenvironment of this study allows for assessing the effect of anti-cancer agents in cancer and stromal cells. This model can be developed to provide a better understanding of tumor immunology.

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